Clinical trial • Phase III • Immunology | Rare Disease
donidalorsen for Hereditary angioedema
Phase III trial of donidalorsen for Hereditary angioedema. open-label. 55 participants.
Overview
- Trial Therapeutic Area
- Immunology | Rare Disease
- Trial Disease
- Hereditary angioedema
- Trial Stage
- Phase III
- Drug Modality
- Oligonucleotide
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 14-03-2024
- First CTIS Authorization Date
- 19-04-2024
Trial design
open-label Phase III trial in Belgium, Bulgaria, France and others.
- Open Label
- Yes
- Target Sample Size
- 55
- Trial Duration For Participant
- 371
Eligibility
Recruits 55 paediatric patients.
- Vulnerable Population
- The protocol selects vulnerable populations and includes adolescents: "Participants and, as applicable, legally authorized representatives (i.e. parent(s)/legal guardian), must provide written and signed informed consent form (ICF)." and "Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent." Age-specific consent/assent documents (parental ICF, assent forms for minors) are provided per country as listed in the ICF document library.
Inclusion criteria
- {"criterion_text":"- 1. Participants and, as applicable, legally authorized representatives (i.e. parent(s)/legal guardian), must provide written and signed informed consent form (ICF).\n- 2. Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g. plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks Open-Label Extension Participants ONLY.\n- 3. Satisfactory completion of ISIS 721744-CS5 (randomized placebocontrolled index study) through Week 25 or participants who are allowed to exit ISIS 721744-CS5 study per protocol with an acceptable safety and tolerability profile New (not previously on donidalorsen) Participants ONLY.\n- 4. Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent.\n- 5. Participants must have a documented diagnosis of HAE-1/HAE-2.\n- 6. Participants must be on a stable dose (≥ 12 weeks) of prophylaxis treatment with lanadelumab or berotralstat or C1-esterase inhibitor prior to the Screening Period."}
Exclusion criteria
- {"criterion_text":"- 1. Have any new condition or worsening of an existing condition or change or anticipated change in medication De-novo Participants.\n- 2. Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III).\n- 3. Anticipated change in the use of concurrent androgen or tranexamic acid prophylaxis used to prevent angioedema attacks Any clinically-significant abnormalities in screening laboratory values.\n- 4. Malignancy within 5 years of Screening, except for non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma that has been successfully treated.\n- 5. Hypersensitivity to the active substance (donidalorsen) or to any of the excipients.\n- 6. Treatment with another investigational drug (non-oligonucleotide) or biological agent within 1 month of Screening or 5 half-lives of investigational agent, whichever is longer.\n- 7. Recent history of, or current drug or alcohol abuse.\n- 8. Participated in a prior donidalorsen study.\n- 9. Exposure to any of the following medications: Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption Oligonucleotides (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Incidence and severity of treatment-emergent adverse events (TEAEs).","definition_or_measurement_approach":""}
Secondary endpoints
- {"endpoint_text":"- 1. The time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 1 to Week 53.","definition_or_measurement_approach":"Investigator-confirmed HAE attacks, normalized per month, measured across Weeks 1–53."}
- {"endpoint_text":"- 2. The time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 5 to Week 53.","definition_or_measurement_approach":"Investigator-confirmed HAE attacks, normalized per month, measured across Weeks 5–53."}
- {"endpoint_text":"- 3. The percentage of Investigator-confirmed HAE attack-free patients from Week 5 to Week 53.","definition_or_measurement_approach":"Proportion of patients without any Investigator-confirmed HAE attacks during Weeks 5–53."}
- {"endpoint_text":"- 4. The time-normalized number of moderate or severe Investigator-confirmed HAE attacks (per month) from Week 5 to Week 53.","definition_or_measurement_approach":"Investigator-confirmed moderate or severe HAE attacks, normalized per month, measured across Weeks 5–53."}
- {"endpoint_text":"- 5. The number of Investigator-confirmed HAE attacks requiring acute therapy from Week 5 to Week 53.","definition_or_measurement_approach":"Count of Investigator-confirmed HAE attacks that required acute therapy during Weeks 5–53."}
- {"endpoint_text":"- 6. Angioedema Quality of Life (AE-QoL) questionnaire total score over 53 weeks.","definition_or_measurement_approach":"Total score on the AE-QoL questionnaire assessed over 53 weeks."}
Recruitment
- Planned Sample Size
- 55
- Recruitment Window Months
- 75
- Consent Approach
- Written, signed informed consent is required from participants and, where applicable, legally authorized representatives (parent(s)/legal guardian). Participants aged ≥12 years provide consent and, when applicable, assent. The documentation set includes age-specific ICFs and assent/parental ICFs (e.g. Adults ICF, 12-14 yr ICF, 15-17 yr ICF, Parental ICF, Assent ICF) and translated materials (documents available in multiple languages such as English, French, Dutch, German, Italian, Spanish, Polish, Bulgarian across country-specific ICFs).
Geography
- Total Number Of Sites
- 23
- Total Number Of Participants
- 55
Belgium
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 22-04-2024
- Processing Time Days
- 18
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Antwerp University Hospital
- Department Name
- Hematology
- Principal Investigator Name
- Didier Ebo
- Principal Investigator Email
- didier.ebo@uza.be
- Contact Person Name
- Didier Ebo
- Contact Person Email
- didier.ebo@uza.be
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 24-04-2024
- Processing Time Days
- 20
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Convex Ltd.
- Department Name
- Medical office of clinical allergology
- Principal Investigator Name
- Anna Dimitrova
- Principal Investigator Email
- anna.valerieva@gmail.com
- Contact Person Name
- Anna Dimitrova
- Contact Person Email
- anna.valerieva@gmail.com
- Site Name
- Alexandrovska University Hospital
- Department Name
- Clinic of clinical allergology
- Principal Investigator Name
- Maria Staevska-Kotasheva
- Principal Investigator Email
- mari66sta@gmail.com
- Contact Person Name
- Maria Staevska-Kotasheva
- Contact Person Email
- mari66sta@gmail.com
France
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 23-04-2024
- Processing Time Days
- 19
- Number Of Sites
- 3
- Number Of Participants
- 4
Sites
- Site Name
- Hopital Saint Antoine
- Department Name
- medecine interne
- Principal Investigator Name
- Delphine Gobert
- Principal Investigator Email
- delphine.gobert@aphp.fr
- Contact Person Name
- Delphine Gobert
- Contact Person Email
- delphine.gobert@aphp.fr
- Site Name
- Grenoble Hospital Center
- Department Name
- medecine interne
- Principal Investigator Name
- Laurence Bouillet
- Principal Investigator Email
- LBouillet@chu-grenoble.fr
- Contact Person Name
- Laurence Bouillet
- Contact Person Email
- LBouillet@chu-grenoble.fr
- Site Name
- Hoptial La Timone
- Department Name
- medecine interne
- Principal Investigator Name
- Stéphane Gayet
- Principal Investigator Email
- stephane.gayet@ap-hm.fr
- Contact Person Name
- Stéphane Gayet
- Contact Person Email
- stephane.gayet@ap-hm.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 22-04-2024
- Processing Time Days
- 18
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Department of Dermatology and Allergology
- Principal Investigator Name
- Markus Alexander Karl Magerl
- Principal Investigator Email
- markus.magerl@charite.de
- Contact Person Name
- Markus Alexander Karl Magerl
- Contact Person Email
- markus.magerl@charite.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Department of Oto-Rhino-Laryngology
- Principal Investigator Name
- Susanne Trainotti
- Principal Investigator Email
- susanne.trainotti@mri.tum.de
- Contact Person Name
- Susanne Trainotti
- Contact Person Email
- susanne.trainotti@mri.tum.de
- Site Name
- Goethe University Frankfurt
- Department Name
- Department for Children and Adolescents
- Principal Investigator Name
- Emel Aygören-Pürsün
- Principal Investigator Email
- emel.aygoeren@kgu.de
- Contact Person Name
- Emel Aygören-Pürsün
- Contact Person Email
- emel.aygoeren@kgu.de
Italy
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 14-05-2024
- Processing Time Days
- 40
- Number Of Sites
- 5
- Number Of Participants
- 13
Sites
- Site Name
- Azienda Ospedale-Universita Padova
- Department Name
- UOSD Allergologia
- Principal Investigator Name
- Mauro Cancian
- Principal Investigator Email
- mcancian@unipd.it
- Contact Person Name
- Mauro Cancian
- Contact Person Email
- mcancian@unipd.it
- Site Name
- Azienda Ospedaliera Universitaria Federico II Di Napoli
- Department Name
- UOC Medicina Interna e Immunologia clinica
- Principal Investigator Name
- Angelica Petraroli
- Principal Investigator Email
- ambulatoriopetraroli@gmail.com
- Contact Person Name
- Angelica Petraroli
- Contact Person Email
- ambulatoriopetraroli@gmail.com
- Site Name
- Istituti Clinici Scientifici Maugeri
- Department Name
- Unità Operativa Medicina Interna ad Indirizzo Geriatrico
- Principal Investigator Name
- Francesca Perego
- Principal Investigator Email
- francesca.perego@icsmaugeri.it
- Contact Person Name
- Francesca Perego
- Contact Person Email
- francesca.perego@icsmaugeri.it
- Site Name
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
- Department Name
- UOC Patologia Clinica – Centro Angioedema Ereditario
- Principal Investigator Name
- Francesco Arcoleo
- Principal Investigator Email
- farcoleo@villasofia.it
- Contact Person Name
- Francesco Arcoleo
- Contact Person Email
- farcoleo@villasofia.it
- Site Name
- Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
- Department Name
- Medicina interna
- Principal Investigator Name
- Francesco Giardino
- Principal Investigator Email
- f.giardino@policlinico.unict.it
- Contact Person Name
- Francesco Giardino
- Contact Person Email
- f.giardino@policlinico.unict.it
Spain
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 22-04-2024
- Processing Time Days
- 18
- Number Of Sites
- 6
- Number Of Participants
- 10
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Allergology
- Principal Investigator Name
- Mar Guilarte Clavero
- Principal Investigator Email
- mguilarte@vhebron.net
- Contact Person Name
- Mar Guilarte Clavero
- Contact Person Email
- mguilarte@vhebron.net
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Allergology
- Principal Investigator Name
- Stefan Cimbollek
- Principal Investigator Email
- scimbollek@gmail.com
- Contact Person Name
- Stefan Cimbollek
- Contact Person Email
- scimbollek@gmail.com
- Site Name
- Hospital Universitario La Paz
- Department Name
- Allergology
- Principal Investigator Name
- Teresa Caballero Molina
- Principal Investigator Email
- mteresa.caballero@salud.madrid.org
- Contact Person Name
- Teresa Caballero Molina
- Contact Person Email
- mteresa.caballero@salud.madrid.org
- Site Name
- Bellvitge University Hospital
- Department Name
- Allergology
- Principal Investigator Name
- Ramon Lleonart Bellfill
- Principal Investigator Email
- rlleonart@gmail.com
- Contact Person Name
- Ramon Lleonart Bellfill
- Contact Person Email
- rlleonart@gmail.com
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Allergology
- Principal Investigator Name
- Leah Landaveri Sánchez
- Principal Investigator Email
- landaveri_lea@gva.es
- Contact Person Name
- Leah Landaveri Sánchez
- Contact Person Email
- landaveri_lea@gva.es
- Site Name
- Hospital Universitario La Paz
- Department Name
- Allergology
- Principal Investigator Name
- Teresa Caballero Molina
- Principal Investigator Email
- mteresa.caballero@salud.madrid.org
- Contact Person Name
- Teresa Caballero Molina
- Contact Person Email
- mteresa.caballero@salud.madrid.org
Netherlands
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 19-04-2024
- Processing Time Days
- 15
- Number Of Sites
- 2
- Number Of Participants
- 12
Sites
- Site Name
- Academisch Medisch Centrum
- Department Name
- Vascular medicine
- Principal Investigator Name
- Danny Cohn
- Principal Investigator Email
- d.m.cohn@amsterdamumc.nl
- Contact Person Name
- Danny Cohn
- Contact Person Email
- d.m.cohn@amsterdamumc.nl
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Internal medicine
- Principal Investigator Name
- Hanneke Oude Elberink
- Principal Investigator Email
- j.n.g.oude.elberink@umcg.nl
- Contact Person Name
- Hanneke Oude Elberink
- Contact Person Email
- j.n.g.oude.elberink@umcg.nl
Poland
- Earliest CTIS Part Ii Submission Date
- 04-04-2024
- Latest Decision Or Authorization Date
- 29-04-2024
- Processing Time Days
- 25
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
- Department Name
- Centrum Alergologii- Poradnia Alergologiczna
- Principal Investigator Name
- Marcin Stobiecki
- Principal Investigator Email
- marcin.stobiecki@uj.edu.pl
- Contact Person Name
- Marcin Stobiecki
- Contact Person Email
- marcin.stobiecki@uj.edu.pl
Sponsor
Primary sponsor
- Full Name
- Ionis Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Sitero LLC
- Responsibilities
- EDC
- Name
- Yprime LLC
- Responsibilities
- ePROs
- Name
- Inclin Inc.
- Responsibilities
- TC: Data Management
- Name
- PPD Development LP
- Name
- Bioclinica Inc.
- Name
- Medpace Finland Oy
- Name
- Marken LLP
- Name
- Emvenio Clinical Research LLC
- Responsibilities
- Home healthcare service
- Name
- FutureMeds GmbH
- Responsibilities
- Home healthcare service
- Name
- Cognizant Worldwide Limited
- Responsibilities
- pharmacovigilance
Third parties
- {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"EDC","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"ePROs","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Inclin Inc.","duties_or_roles":"TC: Data Management","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Quest Diagnostics Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patients reimbursment","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Netherlands","full_name":"Emsere B.V.","duties_or_roles":"Rental equipment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Emvenio Clinical Research LLC","duties_or_roles":"Home healthcare service","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"FutureMeds GmbH","duties_or_roles":"Home healthcare service","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Marken LLP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Cognizant Worldwide Limited","duties_or_roles":"pharmacovigilance","organisation_type":"Non-Pharmaceutical company"}
Investigational products
- Investigational Product Name
- ISIS 721744
- Active Substance
- donidalorsen
- Modality
- Oligonucleotide
- Routes Of Administration
- SUBCUTANEOUS
- Route
- SUBCUTANEOUS
- Maximum Dose
- 80 mg
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